Significant progress has been made over the past few years in identifying new vaccine candidates that could potentially be used for the prevention or immunotherapy of tuberculosis in human beings. The purpose of this proposed project is to take a select few of these vaccine candidates and perform longer term efficacy and safety evaluations to see which are the most robust. The animal model to be used will be the low dose aerosol challenge in the guinea pig, an animal which provides a stringent test given its susceptibility to infection and similarities in immunopathology to human disease. The central hypothesis to be tested will be that different vaccines, given data that their immunologic targets may differ, may behave differently in their ability to modulate, delay, or prevent the development of the disease process. To facilitate this analysis, we will use as a template our recent definition of four discrete phases of the granulomatous process in the lungs of infected guinea pigs, The proposed studies are lengthy, and unavoidably expensive, but should provide a basic framework upon which a standardized procedure for efficacy and safety testing of new tuberculosis vaccines can be based. [unreadable] [unreadable]